PTSD increases risk for major adverse cardiovascular events through neural and cardio-inflammatory pathways.

While posttraumatic stress disorder (PTSD) is known to associate with an elevated risk for major adverse cardiovascular events (MACE), few studies have examined mechanisms underlying this link. Recent studies have demonstrated that neuro-immune mechanisms, (manifested by heightened stress-associated neural activity (SNA), autonomic nervous system activity, and inflammation), link common stress syndromes to MACE. However, it is unknown if neuro-immune mechanisms similarly link PTSD to MACE. The current study aimed to test the hypothesis that upregulated neuro-immune mechanisms increase MACE risk among individuals with PTSD. This study included N = 118,827 participants from a large hospital-based biobank. Demographic, diagnostic, and medical history data collected from the biobank. SNA (n = 1,520), heart rate variability (HRV; [n = 11,463]), and high sensitivity C-reactive protein (hs-CRP; [n = 15,164]) were obtained for a subset of participants. PTSD predicted MACE after adjusting for traditional MACE risk factors (hazard ratio (HR) [95 % confidence interval (CI)] = 1.317 [1.098, 1.580], ß = 0.276, p = 0.003). The PTSD-to-MACE association was mediated by SNA (CI = 0.005, 0.133, p < 0.05), HRV (CI = 0.024, 0.056, p < 0.05), and hs-CRP (CI = 0.010, 0.040, p < 0.05). This study provides evidence that neuro-immune pathways may play important roles in the mechanisms linking PTSD to MACE. Future studies are needed to determine if these markers are relevant targets for PTSD treatment and if improvements in SNA, HRV, and hs-CRP associate with reduced MACE risk in this patient population.

Risks of adverse events in patients with orthostatic intolerance undergoing surgery with general anesthesia.

INTRODUCTION: Orthostatic intolerance (OI) is a group of disorders characterized by symptoms that occur upon standing and resolve with recumbence. Although well established but not widely recognized, these diagnoses may create uncertainty for clinicians dealing with a patient affected by OI and requiring a surgical procedure. OBJECTIVES: To determine the rate of intra- and postoperative major adverse events in patients with OI undergoing surgery with general anesthesia. METHODS: The study was a retrospective study of patients with orthostatic intolerance who underwent surgery requiring general anesthesia from 1 January 2000 to 31 December 2018. RESULTS: A total 171 patients with OI underwent 190 surgeries. In patients with POTS and orthostatic-induced VVS, there were no major significant adverse events. There was one episode of AVNRT in a patient with POTS and one episode of bradycardia secondary to vasovagal reflex in a patient with orthostatic-induced VVS. Moreover, there were 13 (6.8%) episodes of postoperative hypotension. However, the majority of these episodes were related to bleeding, volume depletion or sepsis. All cases of hypotension responded well to appropriate therapy. In patients with OH, the rate of postoperative major adverse cardiac events was 4.7%, and the 30-day mortality rate was 6.1%. This is not significantly different from the calculated risk for patients without OH. There were no myocardial infarctions or deaths at 30 days in patients with POTS or orthostatic-induced VVS. CONCLUSION: Patients with OI may not experience higher rates of perioperative complications compared with patients without OI syndromes.

Anxiety and Depression Associated With Increased Cardiovascular Disease Risk Through Accelerated Development of Risk Factors.

Background: Prior studies have incompletely assessed whether the development of cardiometabolic risk factors (CVDRF) (hypertension, hyperlipidemia, and diabetes mellitus) mediates the association between anxiety and depression (anxiety/depression) and cardiovascular disease (CVD). Objectives: The authors aimed to evaluate the following: 1) the association between anxiety/depression and incident CVDRFs and whether this association mediates the increased CVD risk; and 2) whether neuro-immune mechanisms and age and sex effects may be involved. Methods: Using a retrospective cohort design, Mass General Brigham Biobank subjects were followed for 10 years. Presence and timing of anxiety/depression, CVDRFs, and CVD were determined using ICD codes. Stress-related neural activity, chronic inflammation, and autonomic function were measured by the assessment of amygdalar-to-cortical activity ratio, high-sensitivity CRP, and heart rate variability. Multivariable regression and mediation analyses were employed. Results: Among 71,214 subjects (median age 49.6 years; 55.3% female), 27,048 (38.0%) developed CVDRFs during follow-up. Pre-existing anxiety/depression associated with increased risk of incident CVDRF (OR: 1.71 [95% CI: 1.59-1.83], P < 0.001) and with a shorter time to their development (ß = -0.486 [95% CI: -0.62 to -0.35], P < 0.001). The development of CVDRFs mediated the association between anxiety/depression and CVD events (log-odds: 0.044 [95% CI: 0.034-0.055], P < 0.05). Neuro-immune pathways contributed to the development of CVDRFs (P < 0.05 each) and significant age and sex effects were noted: younger women experienced the greatest acceleration in the development of CVDRFs after anxiety/depression. Conclusions: Anxiety/depression accelerate the development of CVDRFs. This association appears to be most notable among younger women and may be mediated by stress-related neuro-immune pathways. Evaluations of tailored preventive measures for individuals with anxiety/depression are needed to reduce CVD risk.

Radionuclide Imaging of Heart-Brain Connections.

The heart and brain have a complex interplay wherein disease or injury to either organ may adversely affect the other. The mechanisms underlying this connection remain incompletely characterized. However, nuclear molecular imaging is uniquely suited to investigate these pathways by facilitating the simultaneous assessment of both organs using targeted radiotracers. Research within this paradigm has demonstrated important roles for inflammation, autonomic nervous system and neurohormonal activity, metabolism, and perfusion in the heart-brain connection. Further mechanistic clarification may facilitate greater clinical awareness and the development of targeted therapies to alleviate the burden of disease in both organs.

Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk.

BACKGROUND: Chronic stress associates with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (ACl/m) has been linked to lower MACE risk, but the mechanisms are unclear. OBJECTIVES: The purpose of this study was to evaluate whether the association between ACl/m and MACE is mediated by decreased SNA. METHODS: Individuals enrolled in the Mass General Brigham Biobank who completed a health behavior survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography, enabling assessment of SNA. Alcohol consumption was classified as none/minimal, light/moderate, or high (<1, 1-14, or >14 drinks/week, respectively). RESULTS: Of 53,064 participants (median age 60 years, 60% women), 23,920 had no/minimal alcohol consumption and 27,053 ACl/m. Over a median follow-up of 3.4 years, 1,914 experienced MACE. ACl/m (vs none/minimal) associated with lower MACE risk (HR: 0.786; 95% CI: 0.717-0.862; P < 0.0001) after adjusting for cardiovascular risk factors. In 713 participants with brain imaging, ACl/m (vs none/minimal) associated with decreased SNA (standardized beta -0.192; 95% CI: -0.338 to -0.046; P = 0.01). Lower SNA partially mediated the beneficial effect of ACl/m on MACE (log OR: -0.040; 95% CI: -0.097 to -0.003; P < 0.05). Further, ACl/m associated with larger decreases in MACE risk among individuals with (vs without) prior anxiety (HR: 0.60 [95% CI: 0.50-0.72] vs 0.78 [95% CI: 0.73-0.80]; P interaction = 0.003). CONCLUSIONS: ACl/m associates with reduced MACE risk, in part, by lowering activity of a stress-related brain network known for its association with cardiovascular disease. Given alcohol's potential health detriments, new interventions with similar effects on SNA are needed.